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Linking development with generation of novelty in mammalian teeth.

The evolution of mammalian teeth is characterized by the frequent and convergent evolution of new cusps. The evolution of new cusps can be linked to tooth development via population-level variation. This allows testing whether development increases the capacity to evolve, or evolvability, by facilitating and even directing morphological change. In a population sample of living seals, variation in cusp number of individual teeth is from three to five cusps, the variably present cusps being the shortest ones that also develop last. By factoring in recent evidence on development, I show that the variation in cusp number can be explained by a patterning cascade mode of cusp development that cumulatively increases and directs height variation in short cusps. The biased variation in seal tooth cusps supports the recognition of teeth as highly evolvable because only small developmental changes are needed to produce large changes in size and number of small cusps. This evolvability of tooth cusps may have facilitated the fast and independent acquisition of new cusps in mammalian evolution. In phylogenetic studies, small cusps may be unreliable as phylogenetic signals. Population level variation can be a powerful tool in testing and generating hypotheses in developmental evolution studies.

Animals↗

Divergent evolution of fucosyltransferase genes from vertebrates, invertebrates, and bacteria.

On the basis of function and sequence similarities, the vertebrate fucosyltransferases can be classified into three groups: alpha-2-, alpha-3-, and alpha-6-fucosyltransferases. Thirty new putative fucosyltransferase genes from invertebrates and bacteria and six conserved peptide motifs have been identified in DNA and protein databanks. Two of these motifs are specific of alpha-3-fucosyltransferases, one is specific of alpha-2-fucosyltransferases, another is specific of alpha-6-fucosyltransferases, and two are shared by both alpha-2- and alpha-6-fucosyltranserases. Based on these data, literature data, and the phylogenetic analysis of the conserved peptide motifs, a model for the evolution offucosyltransferase genes by successive duplications, followed by divergent evolution is proposed, with either two different ancestors, one for the alpha-2/6-fucosyltransferases and one for the alpha-3-fucosyltransferases or a single common ancestor for the two families. The expected properties of such an hypothetical ancestor suggest that the plant or insect alpha-3-fucosyltransferases using chitobiose as acceptor might be the present forms of this ancestor, since fucosyltransferases using chitobiose as acceptor are expected to be of earlier appearance in evolution than enzymes using N -acetyllactosamine. However, an example of convergent evolution of fucosyltransferase genes is suggested for the appearance of the Leaepitopes found in plants and primates.

Amino Acid Sequence↗

fog-2 and the evolution of self-fertile hermaphroditism in Caenorhabditis.

Somatic and germline sex determination pathways have diverged significantly in animals, making comparisons between taxa difficult. To overcome this difficulty, we compared the genes in the germline sex determination pathways of Caenorhabditis elegans and C. briggsae, two Caenorhabditis species with similar reproductive systems and sequenced genomes. We demonstrate that C. briggsae has orthologs of all known C. elegans sex determination genes with one exception: fog-2. Hermaphroditic nematodes are essentially females that produce sperm early in life, which they use for self fertilization. In C. elegans, this brief period of spermatogenesis requires FOG-2 and the RNA-binding protein GLD-1, which together repress translation of the tra-2 mRNA. FOG-2 is part of a large C. elegans FOG-2-related protein family defined by the presence of an F-box and Duf38/FOG-2 homogy domain. A fog-2-related gene family is also present in C. briggsae, however, the branch containing fog-2 appears to have arisen relatively recently in C. elegans, post-speciation. The C-terminus of FOG-2 is rapidly evolving, is required for GLD-1 interaction, and is likely critical for the role of FOG-2 in sex determination. In addition, C. briggsae gld-1 appears to play the opposite role in sex determination (promoting the female fate) while maintaining conserved roles in meiotic progression during oogenesis. Our data indicate that the regulation of the hermaphrodite germline sex determination pathway at the level of FOG-2/GLD-1/tra-2 mRNA is fundamentally different between C. elegans and C. briggsae, providing functional evidence in support of the independent evolution of self-fertile hermaphroditism. We speculate on the convergent evolution of hermaphroditism in Caenorhabditis based on the plasticity of the C. elegans germline sex determination cascade, in which multiple mutant paths yield self fertility.

Animals↗

Phylogenetic comparison of lens crystallins from the vertebrate and invertebrate--convergent or divergent evolution?

A systematic biochemical comparison has been made of the crystallins isolated from the lenses of five different species belonging to the five major classes of vertebrates. Gel-permeation chromatography of the lens homogenates on Fractogel TSK HW-55(S) revealed well-defined elution patterns with a characteristic distribution of different classes of crystallins from each species. SDS gel electrophoresis and statistical comparison of the amino acid contents indicated that all crystallin groups from different classes share some common subunits and similarity in their amino acid compositions. The results coupled with the relatedness shown in the amino acid compositions of fish gamma-crystallin with those of mammalian gamma-crystallin and the squid crystallin from the invertebrate pointed to the possibility of the existence of a common ancestral protein for all crystallins. This is in favor of the divergent rather than convergent evolution of lens crystallins as commonly assumed in the literature.

Amino Acid Sequence↗

Evolution of flavors and scents.

The world is filled with flavors and scents, which are the result of volatile compounds produced and emitted by plants. These specialized metabolites are the products of specific metabolic pathways. The terpenoid, fatty acid, and phenylpropanoid pathways contribute greatly to production of volatile compounds. Mechanisms that lead to evolution of volatile production in plants include gene duplication and divergence, convergent evolution, repeated evolution, and alteration of gene expression, caused by a number of factors, followed by change in enzyme specificity. Many examples of these processes are now available for three important gene families involved in production of volatile metabolites: the small molecule O-methyltransferases, the acyltransferases, and the terpene synthases. Examples of these processes in these gene families are found in roses, Clarkia breweri, and sweet basil, among others. Finally, evolution of volatile emission will be an exciting field of study for the foreseeable future.

Biological Evolution↗

The natural history of protein domains.

Genome sequencing and structural genomics projects are providing new insights into the evolutionary history ofprote in domains. As methods for sequence and structure comparison improve, more distantly related domains are shown to be homologous. Thus there is a need for domain families to be classified within a hierarchy similar to Linnaeus' Systema Naturae, the classification of species. With such a hierarchy in mind, we discuss the evolution of domains, their combination into proteins, and evidence as to the likely origin of protein domains. We also discuss when and how analysis of domains can be used to understand details of protein function. Unconventional features of domain evolution such as intragenomic competition, domain insertion, horizontal gene transfer, and convergent evolution are seen as analogs of organismal evolutionary events. These parallels illustrate how the concept of domains can be applied to provide insights into evolutionary biology.

Animals↗

Parallel evolution of drug resistance in HIV: failure of nonsynonymous/synonymous substitution rate ratio to detect selection.

Parallel or convergent evolution at the molecular level has been difficult to demonstrate especially when rigorous statistical criteria are applied. We present sequence data from the protease gene from eight patients infected with the human immunodeficiency virus (HIV-1). These patients have been on multiple drug therapies for at least 2 years. We present sequence data from two timepoints: time zero--the initiation of drug therapy--and a subsequent timepoint between 59 and 104 weeks after the initiation of drug therapy. In addition to the sequence data, we present viral load data from both initial and final timepoints. Our phylogenetic analyses indicate significant evolution of virus from initial to final time points, even in three of eight patients who show low viral loads. Of the five patients who escaped drug therapy, identical amino acid replacements were seen in all five patients at two different codon positions, an indication of parallel evolution. We also measured genetic diversity for these patients and found no correlation between genetic diversity and viral load. Finally, we calculated the nonsynonymous and synonymous substitution rates and showed that the ratio of nonsynonymous to synonymous substitution compared to the value of one may be a poor indicator of natural selection.

Anti-HIV Agents↗

Human-like social skills in dogs?

Domestic dogs are unusually skilled at reading human social and communicative behavior--even more so than our nearest primate relatives. For example, they use human social and communicative behavior (e.g. a pointing gesture) to find hidden food, and they know what the human can and cannot see in various situations. Recent comparisons between canid species suggest that these unusual social skills have a heritable component and initially evolved during domestication as a result of selection on systems mediating fear and aggression towards humans. Differences in chimpanzee and human temperament suggest that a similar process may have been an important catalyst leading to the evolution of unusual social skills in our own species. The study of convergent evolution provides an exciting opportunity to gain further insights into the evolutionary processes leading to human-like forms of cooperation and communication.

Animal Communication↗

Tandem repetitive D domains of the sperm ligand zonadhesin evolve faster in the paralogue than in the orthologue comparison.

Gene duplication is regarded as an important evolutionary mechanism creating genetic and phenotypic novelty. At the same time, the evolutionary mechanisms following gene duplication have been a subject of much debate. Here we analyze the sequence evolution of zonadhesin, a mammalian sperm ligand that binds to the oocyte zona pellucida in a species-specific manner. In pig, rabbit, and primates, precursor zonadhesin comprises, among others, one partial and four complete tandem repetitive D domains. The mouse precursor is distinguished by 20 additional partial D3 domains consisting of 120 amino acids each. This gene structure allows sequence comparison in both paralogues and orthologues. Detailed sequence analysis reveals that D domains evolve faster across paralogues than orthologues. Moreover, at the codon level, partial D3 paralogues of mouse show evidence of positive selection, whereas the corresponding orthologues do not. Individual posttranslational motif patterns and positive selection point to neofunctionalization of partial D3 paralogues of mouse, rather than subfunctionalization. However, as we found additional evidence for homogenization by partial gene conversion, sequence evolution of partial D3 paralogues of mouse might be better described as a combination of divergent and convergent evolution. So far, the divergence at the codon level has outbalanced the convergence at the level of smaller fragments. The probable driving force behind the evolutionary patterns observed is sexual selection. We finally discuss whether the functional determination influences the evolutionary regime acting on sperm ligands and egg receptors, respectively.

Amino Acid Motifs↗

Extinction may not be forever.

Here we review the phenomenon of ecomorph evolution and the hypothesis of iterative climatic cycles. Although a widely known phenomenon, convergent evolution has been underappreciated in both its scope and commonality. The power of natural selection to override genealogy to create similar morphologies (even among distantly related organisms) supports classical Darwinian evolution. That this occurs repeatedly in stratigraphically closely spaced intervals is one of the most striking features of Earth history. Periodic extinctions followed by re-evolution of adaptive types (ecomorphs) are not isolated occurrences but are embedded within complex ecological systems that evolve, become extinct, and repeat themselves in temporal synchrony. These complexes of radiation and extinction bundle the biostratigraphic record and provide the basis for a global stratigraphy. At this scale, climatic change is the only mechanism adequate to explain the observed record of repeating faunas and floras. Understanding of the underlying causes may lead to predictive theories of global biostratigraphy, evolutionary processes, and climatic change.

Animals↗

Morphological castes in a vertebrate.

Morphological specialization for a specific role has, until now, been assumed to be restricted to social invertebrates. Herein we show that complete physical dimorphism has evolved between reproductives and helpers in the eusocial naked mole-rat. Dimorphism is a consequence of the lumbar vertebrae lengthening after the onset of reproduction in females. This is the only known example of morphological castes in a vertebrate and is distinct from continuous size variation between breeders and helpers in other species of cooperatively breeding vertebrates. The evolution of castes in a mammal and insects represents a striking example of convergent evolution for enhanced fecundity in societies characterized by high reproductive skew. Similarities in the selective environment between naked mole-rats and eusocial insect species highlight the selective conditions under which queen/worker castes are predicted to evolve in animal societies.

Analysis of Variance↗

The complete cDNA sequence of bovine coagulation factor V.

Lack of availability of a primary structure for bovine factor V has hindered detailed analysis of a vast majority of structure-function correlations on this molecule. To determine the primary structure of bovine factor V, we used liver mRNA as a template for the synthesis of three cDNA libraries. The sequences of seven overlapping cDNA clones infer two bovine factor V variants. Variant 1 results in a 6910-basepair (bp) cDNA including 103 bp of 5'-untranslated sequence, 6633 bp of coding sequence and 171 bp of 3'-untranslated sequence with a putative polyadenylation site. Variant 2 differs only in the size of the coding sequence (6618 bp). The open reading frame translates to factor V consisting of 2211 (or 2206) amino acids including a 28-amino acid signal peptide. Comparison of the amino acid sequences with human factor Va reveals 84% identity for the heavy and 86% for the light chains. In contrast, the B domain (connecting region) exhibits only 59% identity relative to the human molecule. The bovine B domain contains two repeats of a 14-amino acid structure that is contained only once in the human sequence. Bovine factor V lacks one of the nine amino acid repeats and one of the 17 amino acid repeats present in the human B domain. Factor V has little homology to the factor VIII molecule in the B domain. The 17-amino acid repeat missing in bovine factor V allows identification of an 18-amino acid sequence that is homologous to the B domain of human factor VIII. These 18 amino acids may either constitute the unique vestige of a divergent evolution between the B domains of factors V and VIII or reveal the convergent evolution toward a critical epitope involved in the activation of both procofactors.

Amino Acid Sequence↗

NADP-dependent enzymes. II: Evolution of the mono- and dinucleotide binding domains.

Nicotinamide adenine dinucleotides [NAD and NADP with both referred to as NAD(P)] are among the more diffuse redox cofactors. Despite their stereochemical similarity where the only difference is a phosphomonoester on the ribose near the adenine of NADP, they show different biochemical reactivities with NAD behaving as an oxidant and NADP as a reductant. NAD(P)-dependent enzymes generally share a common open alpha/beta fold with few exceptions only recently structurally characterized. This study of the molecular evolution of the NAD(P) binding domains, possible given the large number of known molecular structures, addresses two main questions: 1) can a common fold exist in different biological systems (divergent evolution) and 2) does a relationship exist among similar biological systems that display different folds (convergent evolution)? Both the structures of mono- and dinucleotide binding domains have been classified by cluster analysis based on the similarity evaluated by their main chain C alpha superposition. Moreover, the cofactor conformations and the stereochemical characteristics of their pockets have also been classified by analogous methods on the basis of the published tertiary structures. Two primary results appear: 1) the classification of the mononucleotide binding domains is different from that of the dinucleotide binding folds and 2) both divergent and convergent evolutionary pathways can be hypothesized, the latter less frequently observed and less pronounced but nevertheless evident. The generally accepted hypothesis that dinucleotide binding domains have evolved by gene duplication of primordial genes coding for the smaller mononucleotide binding domains is acceptable but the two halves of the resulting dinucleotide binding domains are evolutionarily uncorrelated. The NH2-terminal mononucleotide binding domain is less variable than the COOH-terminal half, probably because it involves the binding of the ADP moiety of NAD(P) invariant in all examined systems. There is evidence to postulate that evolutionary pathways for NAD(P)-dependent enzymes are both divergent and convergent. In fact, nearly all combinations of similarity dissimilarity in overall fold, cofactor conformation, and cofactor binding pocket structural characteristics for each enzyme pair examined are possible. The NAD(P)-dependent enzymes apparently provide a canonical example of an evolutionary principle that "anything goes."

Animals↗

Enhancer activity of upstream hypersensitive site 2 of the chicken beta-globin cluster is mediated by GATA sites.

Upstream of the chicken beta-globin gene cluster are four DNase I-hypersensitive sites (HS1-4). Hypersensitive sites located upstream of the mammalian beta-globin clusters have enhancer activity and mediate position-independent gene expression. In contrast, a region inside the chicken cluster has enhancer activity and mediates position-independent expression. Here we investigate the function of the chicken upstream sites, which are different from the mammalian ones in sequence, number, and distance from the genes. Each was tested for its effect on reporter gene expression in transfected primary erythroid cells. HS2 and HS3 (4.4 and 6.4 kilobases upstream of rho-globin) showed significant enhancer activity while HS1 and HS4 (1.6 and 11 kilobases upstream of rho-globin) did not. A 237-base pair region of HS2 contained the sequences necessary for enhancer activity. Proteins from erythroid extracts bound HS2 in seven different regions; six of these sites were characterized. GATA-1 bound to four of the sites. Each site contributed to the enhancer activity of HS2. Two other sequences bound proteins that may be related to Sp1 and erythroid krüppel-like factor. Surprisingly, mutations in these elements, which disrupted protein binding, did not affect enhancer activity. Thus, the observed enhancer activity of HS2 is due to the four GATA sites. The existence of multiple GATA sites in both chicken HS2 and the mammalian upstream sites may be due to evolution from a common element with preservation of only very short sequences or to convergent evolution. These observations highlight the crucial role for GATA proteins in globin regulation.

Amino Acid Sequence↗

Blood-feeding arthropods: live syringes or invertebrate pharmacologists?

The habit of blood feeding evolved independently several times among the > 14,000 species and 400 genera of hematophagous arthropods. The specific need to remove blood from the host's skin led to sophisticated mechanical adaptations in invertebrate mouthparts. Moreover, the need to counteract the vertebrate host's hemostasis led to the evolution of salivary antihemostatic compounds injected into the host by these same mouthparts. The convergent evolution scenario for hematophagy has resulted in a large diversity of salivary anticlotting, antiplatelet, and vasodilatory substances. Thus, in addition to excelling as phlebotomists, hematophagous arthropods excel as pharmacologists.

Animals↗

A metabolic node in action: chorismate-utilizing enzymes in microorganisms.

The shikimate pathway has been described as a metabolic tree with many branches that led to the synthesis of an extensive range of products. This pathway is present only in bacteria, fungi, and plants. While there is only little difference in the sequence of the chemical reactions of the pathway, significant differences exist in terms of organization and regulation. In the main trunk of the shikimate pathway, D-erythrose 4-phosphate and phosphoenolpyruvate are converted via shikimate to chorismate. Chorismate is the common precursor for the biosynthesis of the aromatic amino acids, phenylalanine, tyrosine, and tryptophan, but also for other products as diverse as folate cofactors, benzoid and naphthoid coenzymes, phenazines, and siderophores. Five chorismate-utilizing enzymes have been characterized in microorganisms: chorismate mutase, anthranilate synthase, aminodeoxychorismate synthase, isochorismate synthase, and chorismate pyruvate-lyase. In this review these enzymes are discussed in terms of the corresponding gene structures and regulation, nucleotide and protein sequences, protein structures, and reaction mechanisms. The main emphasis is on transcriptional and posttranslational regulatory mechanisms, in view of how a microbial cell exploits its chorismate pool in diverse anabolic pathways. Comparison of the chorismate-utilizing enzymes has shown that some of them share sequence similarity, suggesting divergent evolution and commonality in reaction mechanisms. However, other chorismate-utilizing enzymes are examples of convergent evolution toward similar reaction capabilities.

Anthranilate Synthase↗

Analysis of the allelic diversity of the mycobacterial interspersed repetitive units in Mycobacterium tuberculosis strains of the Beijing family: practical implications and evolutionary considerations.

A study set comprised 44 Mycobacterium tuberculosis strains of the Beijing family selected for their representativeness among those previously characterized by IS6110-RFLP and spoligotyping (Northwest Russia, 1997 to 2003). In the present study, these strains were subjected to mycobacterial interspersed repetitive units (MIRU) typing to assess a discriminatory power of the 12-MIRU-loci scheme (P. Supply et al., J. Clin. Microbiol. 39:3563-3571, 2001). The 44 Russian Beijing strains were subdivided into 12 MIRU types with identical profiles: 10 unique strains and two major types shared by 10 and 24 strains. Thus, basically, two distinct sublineages appear to shape the evolution of the Beijing strains in Russia. Most of the MIRU loci were found to be (almost) monomorphic in the Russian Beijing strains; the Hunter-Gaston discriminatory index (HGDI) for all 12 loci taken together was 0.65, whereas MIRU26 (the most variable in our study) showed a moderate level of discrimination (0.49). The results were compared against all available published MIRU profiles of Beijing strains from Russia (3 strains) and other geographic areas (51 strains in total), including South Africa (38 strains), East Asia (7 strains), and the United States (4 strains). A UPGMA (unweighted pair-group method with arithmetic averages)-based tree was constructed. Interestingly, no MIRU types were shared by Russian and South African strains (the two largest samples in this analysis), whereas both major Russian types included also isolates from other locations (United States and/or East Asia). This implies the evolution of the Beijing genotype to be generally strictly clonal, although a possibility of a convergent evolution of the MIRU loci cannot be excluded. We propose a dissemination of the prevailing local Beijing clones to have started earlier in South Africa rather than in Russia since more monomorphic loci were identified in Russian samples than in South African samples (mean HGDI scores, 0.08 versus 0.17). To conclude, we suggest to use a limited number of MIRUs for preliminary subdivision of Beijing strains in Russian (loci 26 + 31), South African (10 + 26 + 39), and global settings (10 + 26 + 39).

Alleles↗

Balancing under constraint: Structural insights into norovirus evolution and antigenic innovation.

Norovirus is the leading cause of acute viral gastroenteritis worldwide. While genomic studies have revealed its diversity and evolutionary patterns, the structural mechanisms driving viral adaptation remain poorly understood. Here, we establish a comprehensive structural database of norovirus VP1 P-domains across nine genogroups (GI-GIX) through large-scale AlphaFold2 predictions. By integrating phylogenetic analysis of VP1 sequences and structures, we demonstrate that sequence and structural evolution show overall concordance under purifying selection, yet significant local discrepancies reveal distinct patterns of convergent evolution shaped by structural constraints and functional divergence. Focusing on the predominant GII.4 genotype, we found that compared to near-full-genome and nucleotide trees, only the VP1 amino acid tree reliably clustered GII.4 variants in chronological order as monophyletic groups. We further identify a hierarchical evolutionary strategy: positive selection may drive structural hypervariability in major antigenic epitopes D and C for immune escape, with epitope D exhibiting pronounced structural flexibility that complicates its structural characterization, whereas coevolutionary analysis uncovers a broad network of compensatory interactions spanning multiple epitopes, with striking enrichment in epitope A. These epitopes exhibited a pattern of "sequence plasticity with structural conservation", maintained by coevolutionary constraints that preserve conformational integrity. Together, these findings suggest that norovirus vaccine strategies targeting the structurally conserved conformations of epitopes A and G could overcome the limitations of traditional strain-specific approaches, offering a pathway toward broad protection against evolving viral diversity.

Norovirus↗